Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer.
Carcinogenic heavy metals replace Ca2+ for DNA binding and annealing activities of mono-ubiquitinated annexin A1 homodimer.
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致癌重金属取代 Ca2+ 参与单泛素化膜联蛋白 A1 同二聚体的 DNA 结合和退火活性。
DOI：
10.1016/j.taap.2010.07.005
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发表时间：
2010
影响因子：
3.8
通讯作者：
Hirata,Fusao
中科院分区：
文献类型：
--
作者：
Hirata,Aiko;Corcoran,GeorgeB;Hirata,Fusao
从大鼠肝细胞核中纯化了单泛素化的膜联蛋白A1。单泛素化膜联蛋白A1的同源二聚体形式能够以Mg 2+和ATP依赖的方式解链dsDNA，并以Ca 2+依赖的方式退火ssDNA。磷脂降低了最大退火活性所需的Ca 2+浓度。重金属如As 3+、Cr 6+、Pb 2+和Cd 2+取代了Annexin A1与ssDNA结合和退火活性中的Ca 2+。虽然这些金属抑制解旋的dsDNA核膜联蛋白A1在Mg 2+和ATP的存在下，他们增强dsDNA依赖的ATP酶活性的膜联蛋白A1。重金属可能通过DNA退火反应产生了dsDNA，这是DNA解旋反应的底物。从指数生长的L5178 Y tk（+/-）小鼠淋巴瘤细胞中分离DNA合成体，发现其含有解旋酶活性。As 3+或Cr 6+诱导的DNA合成体ssDNA结合活性的增加被单特异性抗膜联蛋白A1抗体降低，但不被抗Ig抗体降低。抗annexin A1抗体也阻断了As 3+或Cr 6+对DNA合成体的DNA解旋和退火活性的抑制和刺激作用。基于这些观察，可以得出结论，重金属对DNA退火和解旋活动的影响是介导的，至少在很大程度上，通过单泛素化的膜联蛋白A1同源二聚体的行动。
Mono-ubiquitinated annexin A1 was purified from rat liver nuclei. The homodimer form of mono-ubiquitinated annexin A1 was able to unwind dsDNA in a Mg2+- and ATP-dependent manner, and to anneal ssDNA in a Ca2+-dependent manner. Phospholipids decreased the concentration of Ca2+required for maximal annealing activity. Heavy metals such as As3+, Cr6+, Pb2+and Cd2+substituted for Ca2+in the ssDNA binding and annealing activities of annexin A1. While these metals inhibited the unwinding of dsDNA by nuclear annexin A1 in the presence of Mg2+and ATP, they enhanced dsDNA-dependent ATPase activity of annexin A1. Heavy metals may have produced dsDNA, a substrate for the DNA unwinding reaction, via the DNA annealing reaction. DNA synthesomes were isolated from L5178Y tk(+/−) mouse lymphoma cells in exponential growth, and were found to contain helicase activities. The As3+- or Cr6+-induced increases in ssDNA binding activity of DNA synthesomes were reduced by a mono-specific anti-annexin A1 antibody, but not by anti-Ig antibody. Anti-annexin A1 antibody also blocked the inhibitory and stimulatory effects of As3+or Cr6+towards DNA unwinding and annealing activities of DNA synthesomes. Based on these observations, it can be concluded that the effects of heavy metals on DNA annealing and unwinding activities are mediated, at least in substantial part, through actions of the mono-ubiquitinated annexin A1 homodimer.